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The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 ( w / w / w ). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.

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Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol